The enzyme carbonic anhydrase (CA) (EC 4.2.1.1) is a metalloenzyme (which is an enzyme that includes one or more functional metal atoms) that catalyzes the rapid conversion of carbon dioxide into bicarbonate via a hydration reaction. The catalytic center of the enzyme consists of a Zinc atom coordinated by three histidine residues in the active site in addition to a water molecule that serves as a source of hydroxide ion. Over the years, a number of catalytic systems have been designed in hopes to mimic CA's active site and thus use these synthetic systems to effect the removal of carbon dioxide from the atmosphere and the environment. These efforts have resulted in a number of catalysts possessing the Zinc-bound water molecule and capable of catalyzing the hydration of carbon dioxide with varied efficiency; however, the catalysts still suffer from several drawbacks.
One such drawback lies in the synthetic protocols utilized for the construction of these prior art catalysts, which do not enable a library of Zinc-coordinating scaffolds to be generated for the rapid evaluation and assessment of their catalytic properties. As such, even if a potentially good catalyst candidate may be identified, there are no simple means to chemically modify its structure to further improve its catalytic profile. Furthermore, the catalysts described to date originate from synthetic routes plagued with time consuming purification techniques and the inaccessibility to generate chemical diversity within a designed system since each catalyst is manufactured through the same amount or more steps as the other, with no common intermediate that can be used for scale up production.
Another drawback to these prior art catalysts is the poor to non-existent water-solubility of the catalysts, as reported in literature so far, thus preventing a direct comparison of the catalyst's attributes to those of the active site of CA. Additionally, another drawback is the experimental evidence that the zinc-bound water molecule must possess a pKa value close to that one exhibited by the CA enzyme (pKa of about 7.0) to efficiently catalyze the hydration reaction. This key property of a designed catalytic system finds no benefit from the current, restricted synthetic schemes employed for their construction.
Therefore, it would be beneficial to have the ability to prepare a library of diverse scaffolds to construct catalysts, not only to study the catalysts produced, but to directly tune the value of the water's pKa in the produced catalyst by altering the electronic properties of the triazole rings bound to the Zinc metal via analog synthesis.